Hydrochloric Acid → trans-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3-(trifluoromethyl)benzyl)piperidine-1-carboxylate

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Reaction Steps

A solution of trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3-(trifluoromethyl)benzyl)-piperidine-1-carboxylate (1.8 g, 4.33 mmol) (from example 107, step 1) in MeOH (7 mL) was added to a solution of NaOH (225 mg, 5.63 mmol) in MeOH/H2O (8 mL/0.5 mL) at −30° C. After 10 min hydroxylamine hydrochloride (0.602 g, 8.67 mmol) and NaOH (347 mg, 8.67 mmol) were added in MeOH (7 mL) and H2O (7 mL). Stirring was continued at −30° C. for 30 min. The reaction solution was poured into 6 M HCl (60 mL) at 80° C. and heated for 30 min. The reaction mixture was dissolved between water and ethyl acetate. The organic phase was isolated, dried with Na2SO4, filtered through celite and the solvent was evaporated. Purification using prepLC (pH=3, large column 25-55% MeCN over 20 min) Trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3-(trifluoromethyl)benzyl)piperidine-1-carboxylate (1.06 g, 63.6%) was isolated. 1H NMR (400 MHz, cdcl3) δ 1.49-2.17 (m, 4H), 2.80-3.22 (m, 4H), 3.34-3.76 (m, 3H), 4.07-4.40 (m, 1H), 4.52-4.84 (m, 1H), 5.65 (s, 1H), 7.28-7.54 (m, 4H). MS m/z 385 (M+H)+

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